1. Field of the Invention
The present invention relates generally to a device and method for delivering a pharmacological agent to the body, and more particularly, to a device and method for stimulating penile erection using a pharmacological agent.
2. Related Art
The field of male sexual dysfunction has witnessed dramatic improvements in the diagnosis and the management in the last decade. Attempts to discover aphrodisiacs and endeavors to improve sexuality appear to have been an inherent trait of mankind throughout the ages. Since the dawn of time, man has strived to combat the impotence with various medication. It is only recently that these efforts have borne some fruit.
Impotence affects nearly 10 million men in the Unites States. It creates mental stress and the sociologic distress both in the patient and his partner. Historically, the initial concern in the evaluation of an impotent man was to differentiate between psychogenic and organic impotence. In 50's and 60's the psychogenic impotence was considered to be the most common cause accounting for up to 90% of the cases. The advent of sophisticated technology has lead to critical discoveries in understanding of erectile function. The development of sensitive diagnostic armamentarium has made it possible to pinpoint an organic (and probably a treatable) cause in about 90% of the cases.
The penis consists of urethra and three erectile bodies: two corpora cavernosa and a corpus cavernosum. All of these structures have their own fascial sheaths and together they are covered with skin. Each corpus cavernosum has a thick fibrous layer, the tunica albuginea. The two corpora cavernosa constitute the main erectile tissue. Although they are depicted as separate bodies, they communicate with each other across the midline septum and act as a single erectile unit. They are filled with the helicine arteries, venous sinusoid, ventiles and emissary veins, nerves, muscle fibers, and trabeculae arising from the tunica albuginea. Close to the pubic symphysis the corpora split to from the crurae which are attached to the ischio-pubic rami.
The corpus spongiosum lies in the groove between the two corpora cavernosa on the ventral aspect. Its tunica albuginea is thin and at its distal end it expands to form the glans. Although it has erectile tissue it contributes only a little in the clinically significant erection. The urethra traverses through the entire length of the corpus spongiosum.
The three corpora are covered with deep fascia (Buck's fascia) that encloses the set of deep neuro-vascular structure. The superficial set of vessels, e.g., the dorsal vein of penis lies between the deep and the superficial fascia (Dartos fascia).
The skin of the penis is hairless. There are however sebaceous glands in the corona, the overhang rim of the glans, and the coronal sulcus that produce secretions called smegma. In an uncircumcised individual the redundant skin covers the glans as foreskin.
The blood supply of skin of the penis comes from the right and left inferior external pudendal vessel from the femoral arteries. The deeper structures are supplied by the common penile artery which is the continuation of the internal pudendal artery after it has given off the perineal branch. The emissary veins follow an oblique course through the tunica albuginea to drain into the deep dorsal veins which in turn drains into the prostatic (Santorini's) plexus. Three to four veins from the crura drain in to internal pudendal veins.
Penile erection is a complex phenomenon involving several factors. The animal and human studies have shown that the hemodynamic changes during erection consist of relaxation of smooth muscle of the arteriole and sinusoids, decreased resistance to blood flow; increased blood flow to the corpora cavernosa; expansion of lacunae of the sinusoid and distension of the tunica albuginea, compression of the ventiles and the emissary veins resulting in venous occlusion, increased pressure in the corpora cavernosa and penile erection.
These changes are mediated by neurotransmitters. The parasympathetic stimulation lead to erection by vasodilatation and the sympathetic stimulation causes detumescence by vasoconstriction. Acetylcholine, the cholinergic neurotransmitter, is presumed to act pre-junctionally leading to the release of a variety of still debated chemical mediators at the penile vascular smooth muscle neuromuscular junction. These mediators include nitric oxide, nonadrenergic noncholinergic neurotransmitter, vasoactive intestinal peptide and prostaglandin E.sub.1.
Impotence is defined as failure to achieve and/or maintain erection sufficient for intercourse. Arbitrarily, repeated occurrence of this symptom for at least six months or more requires treatment.
For decades, impotence was associated with psychogenic causes. Organic etiology was first linked to sexual dysfunction in about 1923. At that time, it was still emphasized that the psychogenic etiology was the primary cause and that only 5% of impotence cases were secondary to organic diseases. With improved technologies in the area of diagnosis today, an organic cause can be found in most cases. Neurogenic, endocrinologic, and vasculogenic abnormalities account for 85% of impotence cases. Other causes include drugs and failure of the erectile tissue, e.g. Peyronie's disease. Psychogenic impotence makes only a small portion of the impotent population. The most common clinical conditions associated with erectile dysfunction include diabetes mellitus and hypertension.
The following methods are being presently practiced to treat the erectile dysfunction: Oral agents; Topical agents (Transcutaneous and transurethral); Hormones; Vacuum therapy; Intracavernous injection; and Penile prosthesis.
Oral agents, such as yohimbine chloride, an indole alkaloid derived from the bark of yohimbehe tree, has been considered an aphrodisiac for centuries in the western world. Scientific evaluation with double blind, placebo controlled studies has been performed only recently. These studies have shown a complete response of 20%, partial response of 23% and a failure rate of 57%.
Topical agents, such as nitroglycerin (NTG), a drug used for coronary artery disease for decades, has been used recently for the treatment of impotence. Aqueous based gel has been found to be rapidly absorbed through the penile skin. The mechanism of action is probably related to its ability to donate the nitric oxide (NO). Other NO donors, e.g., minoxidil have also been tried. Variable response rates have been published.
The advantage of the topical treatment is its ease of use and non-invasiveness. The quality of erection is poor. In addition it is associated with side effects, e.g., burning, headache, postural hypotension, syncope arid spousal headache via transvaginal absorption. Recently prostaglandin E.sub.1 suppositories have been used transurethrally to produce erection. A multicenter trial is presently being carried out in the United States to assess the safety and the efficacy of this method.
Hormones, such as testosterone, given intra-muscularly in patients with low testosterone levels in the absence of other causes of erectile dysfunction may be helpful.
Vacuum therapy devices consist of a plastic cylinder, vacuum pump, connector tubing and elastic constriction band. Erection is achieved by creating negative pressure with the pump in the cylinder (which is applied on the penis), and maintained with the constriction band applied to base of the penis. Response rate of more than 90% has been reported. The device is relatively inexpensive and safe. The erection however is cold with a drop of penile skin temperature by 0.96.degree. C. (the negative pressure produces pain and petechiae. Pain is also produced due to constricting band. The penis proximal to the constriction band is soft and pivots at the base. The major drawback is the lack of spontaneity.
Intracavernous injection is the modern pharmacological treatment and consists of injecting a vasoactive agent into the penis (corpus cavernosum) with a needle and a syringe under aseptic condition. The steps of treatment includes finding an optimum dose for an individual patient, educating the patient about the penile anatomy, and imparting training to inject with a sterile technique and self injection at home. It requires manual dexterity and bodily habitus which should not obstruct the patient's view of the penis as encountered in morbidly obese subjects.
Different medicines have been tried e.g., papaverine, phenoxybenzamine and prostaglandin E.sub.1. Erection is achieved secondary to smooth muscle relaxation resulting in increased blood flow to the corpora cavernosa. Response rate of 80-100% have been achieved depending on the underlying cause. The quality of erection is very close to natural; it is warm and hard. The side effects include priapism, hematoma, inadvertent injection into the urethra, fibrosis, penile atigulation and parasthesias. Many patients (and their partners) refuse this modality due to needle phobia even those who use it suffer from the stigma of carrying a needle and syringe. Many patients complain of the lack of spontaneity and interruption of foreplay to inject.
Penile prosthesis or implants are placed in the corpus cavernosum. They are mainly of two distinct types: the malleable or the rigid prosthesis and multi-component inflatable prosthesis. The inflatable prosthesis have cylinders that are placed in the corpora cavernosa surgically. These are connected to reservoirs containing fluid. Erection is achieved by compression of the reservoir or a mechanical valve which leads to transference of fluid from the reservoir to the cylinders.
When properly implanted and limitation of the prosthesis are understood a very gratifying result is the norm. The quality of the erection is excellent in terms of rigidity but skin is cold. These device shave high mechanical failure rate. The complication include perforation of the corpora cavernosa, erosion, cylinder crossover, infection, penile curvature and glans bowing penile necrosis. The disadvantage of the procedure is the irreversibility and the need for major surgery. Additionally, such implants involve gross insult to the corpus cavernosum.
There remains a need for an improved device and method of treating male impotence. Moreover, a need remains for a device and method for causing penal erection in a more natural manner without interruption of sexual activity.